V₂C-Driven Nanodelivery Platform Potentiates Synergistic Breast Cancer Therapy

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Conventional therapies for TNBC are limited by several drawbacks, including poor therapeutic efficacy and adverse effects. In contrast, photothermal therapy (PTT) has shown advantages in the treatment of TNBC due to its ease of administration and safe profile. Vanadium carbide (V 2 C), a new type of two-dimensional nanomaterial used in biomedicine, has shown excellent photothermal conversion and drug-carrying properties and has proven to be safe owing to its biodegradable characteristics. Therefore, in this study, the chemotherapeutic drug doxorubicin (Dox) was loaded onto V 2 C to prepare a new nanocomposite (V 2 C–Dox nanosheets). PTT with V 2 C–Dox induced localized therapeutic thermal effects and prompted drug release. V 2 C and V 2 C–Dox nanosheets alone were nontoxic to breast cancer cells. However, Dox, V 2 C+laser, and V 2 C–Dox+laser significantly inhibited the viability, clonogenic ability, and migration of breast cancer cells and induced their apoptosis, with V 2 C–Dox+laser having the strongest effect. In addition, combined transcriptomic and metabolomic analyses indicated that the amino acid biosynthesis pathway and the ferroptosis pathway resulting from the aberrant expression of SLC7A11, PED4D, and 2-oxo-4-hydroxy-4-carboxy-5-uronium imidazoline may be involved in the antibreast cancer effects of V 2 C–Dox after irradiation. Experiments in a breast cancer xenograft model showed that V 2 C–Dox@Gel significantly inhibited tumor growth following irradiation without inducing toxic side effects. Therefore, V 2 C–Dox@Gel, as a novel, controllable nanodelivery system for combined PTT and chemotherapy, could synergistically improve therapeutic efficacy in TNBC without causing adverse effects. Thus, it has immense potential as a therapeutic agent for TNBC.